Vicentini, F. A. | Search bioRxiv

bioRxiv2025

Early-life gut microbiome and stress-axis perturbations dysregulate systemic, mucosal, and brain immunity

BackgroundEarly-life disruptions to the gut microbiome and stress-axis significantly influence the development of immune, neuroendocrine, and other physiological systems. However, the precise microbial species and pathways mediating these effects remain poorly characterized. Using a murine model, we investigated the individual and combined effects of early-life antibiotic exposure and chronic stress on gut microbiota composition, short-chain fatty acid (SCFA) production, hypothalamic-pituitary-adrenal (HPA) axis activity, and systemic, mucosal, and neuroimmune responses. ResultsBroad-spectrum antibiotic treatments severely reduced microbial diversity and SCFA concentrations, with changes persisting into adulthood. Chronic early-life stress exerted more modest but notable effects, reducing key SCFA-producing taxa and impacting microbiome metabolic output. Combined disruptions led to altered microglial active phenotype and cytokine profiles, impaired immune cell populations, and suppressed HPA axis activity. Multi-omic correlational analyses revealed strong associations between SCFAs, specific gut microbes, and immune responses, implicating SCFAs as critical mediators of gut-brain communication. Notably, antibiotic exposure exacerbated susceptibility to allergic airway inflammation, highlighting the systemic consequences of early-life microbiome disturbances. ConclusionsThese findings demonstrate that early microbial perturbations impair neuroimmune maturation, HPA axis regulation, and host resilience to inflammatory diseases. Our study underscores the importance of preserving the early-life microbiome to support long-term immune and neurodevelopmental health, offering insights into potential therapeutic interventions for mitigating the impact of early-life microbiota disruptions.

microbiology↗

bioRxiv2019

Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice

Gut microbiomes make major contributions to the physiological and immunological development of the host, but the relative importance of their bacterial and fungal components, and how they interact, remain largely unknown. We applied carefully controlled experiments in gnotobiotic mice colonized with defined communities of bacteria, fungi, or both to differentiate the direct role of fungi on microbiome assembly, host development, and susceptibility to colitis and airway inflammation. Our results revealed that fungal colonization alone was insufficient to promote the intestinal anatomic and physiological changes seen in mice colonized by bacteria, and had limited impact on the fecal metabolome. However, fungal colonization promoted major shifts in bacterial microbiome ecology, and had an independent effect on the innate and adaptive immune development in young mice. Fungi further exacerbated some aspects of the inflammatory effects of the bacterial community during OVA-induced airway inflammation by promoting macrophage infiltration in the airway. Our results demonstrate a dominant ecological and physiological role of bacteria in gut microbiomes, but highlight fungi as an ecological factor shaping the assembly of the bacterial community and a direct capacity to impact immune system and modulate disease susceptibility. These findings demonstrate that studies focused on bacteria alone provide an incomplete portrayal on microbiome ecology and functionality, and prompt for the inclusion of fungi in human microbiome studies.

microbiology↗